Antimicrobial suture for medical use with grapefruit extract, and manufacturing method thereof

ABSTRACT

There is provided an antimicrobial suture for medical use characterized in that the suture contains the grapefruit extract, and a manufacturing method thereof. The antimicrobial suture for medical use of the present invention may prevent from the pathogen infection being occurred by which the suture contains the grapefruit extract having the antimicrobial effect and provide the antimicrobial effect.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the priority of Korean Patent Application No. 2009-0121725, filed on Dec. 9, 2009, in the Korean Intellectual Property Office, the disclosure of which is incorporated herein by reference.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to an improvement of antimicrobiosis of a biodegradable or non-biodegradable suture being used in the surgery, and more particularly, to an improvement of antimicrobiosis of a suture with a functional material being included in the grapefruit extract by impregnating the suture into the grapefruit extract having an antibiotic effect.

2. Description of the Related Art

A suture is an important joining material for medical use being used in order to keep together and place the cut site of surgery at the normal position until the wound is healed. The requirements that the suture must meet include excellent biocompatibility, chemical stability, flexibility, durability, thermal resistance, deteorative property, formability, processability and inexpensive production cost.

The examples of the suture include an absorptive suture and unabsorptive suture, the absorptive suture includes a catgut and a collagen which are natural suture, PGA (polyglycolic acid) and PLA (polylactic acid) which are synthetic suture, and the unabsorptive suture includes polyester, nylon, and the like.

The history of the suture for medical use starts from the documentation that the gippies used tendon or cord for the suture 5,000 years ago, then through the Rome, the middle ages and the modern, the bioabsorptive suture was developed for the first time from the kidskin and deerskin by Pennsylvania medical college in 1806. Later, the synthetic suture have developed and used since 50 years ago and recently have produced in the various form such as the form of much firm clip with bioabsorbance.

Meanwhile, the biodegradable suture widely used the catgut being made of the organ extracts of animals such as cattle or sheep before 1970s, however the use had been gradually decreased with technology deterioration due to the low strength, side effects generation due to the tissue reaction, and the like. The catgut is originated from the use of the entrails of cat merely, the surgical suture which is made of the synthetic fiber being degraded and absorbed itself by which the ester group of polymer is hydrolysed with the body fluid in the human tissue have been steadily developed after 1970s.

The synthetic suture may be largely classified from PGA (polyglycolic acid) suture being made by twisting several threads and PDO (polydioxanone) suture being made of single thread. The PDO suture has the decreased flexibility and elasticity because of the single strand, but its surface is even and there is no space among the threads to reduce the bacterial infections, however PGA suture has the advantage that the excellent felxcibility and elasticity because it is made by twisting several threads, but the disadvantage that its surface is rough and there is the space among the threads to be prone to bacterial infection.

A PGLA (poly(glycolide-co-L-lactide) suture that is developed as the was for making up the disadvantage of the two types of suture has good flexibility and elasticity because it is a copolymer which is copolymerized by using glycolide and lactide as the raw material, and may reduce the roughness of the surface by making the coating efficiency better by using calcium stearate as coating agent on the surface.

In addition, the biodegradation period of the PGA, PLA homopolymer somewhat depends on the molecular weight, but usually is more than 1 year, however PGLA that is their copolymer is biodegraded for several weeks to scores of weeks depending on the molecular weight.

The requirements which such various sutures must have include suitable tension and elasticity without occurring the reaction within the tissue, and the suture should not provide the circumstance that virus may grow.

In addition, the suture should not induce allergy and the hypersensitive reaction, or should not be carcinogenic, should be convenient to use, have good cutting force after knotting without easy untying and snapping of the knot or strand, and should not go bad their form or component when disinfecting with High Pressure Sterilization. Meanwhile, a certain amount of strength should be maintained in order to be possible the maintenance during the required period for agglutination of the tissue because the reforming of the scar is slowly made.

Thus, the biodegradable suture must be convenient to use itself, furthermore the case of infection being capable of occurring at the time of the surgery should be also considered.

As the way for resolving the problem of secondary infection due to the suture, the materials having the antibiotic, effects such as a nano-silver material have been traditionally used in order to give the antimicrobial activity to the suture. However, such nano-particle materials had the problem that it remains in the body for a long period when entering the body.

Meanwhile, a Naringin component that is one of the components of the grapefruit extract is a kind of a flavonoid component being known to Vitamin P having the antibiotic effect, is merely in the peel and seed of the well ripen grapefruit, and tastes bitter. The molecular formula is C₂₇H₃₂O₁₄2H₂O and the chemical structure is as following chemical formula 1:

Looking into the major functions of a narangin, the narangin has the bacteriostatic effect of stopping the growth of the microorganism in the food and the antibiotic effect of sterilizing the microorganism. In addition, the narangin acts as an antioxidant, and a strong natural antioxidant having better effect than a fat-soluble tocopherol in the food. In particular, it is characterized in that it is water-soluble so that the range of being used is wide, and is nontoxic even when highly intaking.

Shortly looking into the principle of the antioxidation action of a naranjin, it is as following chemical formula 2:

In addition, the narangin component acts as a metal chelator to prevent the action of enzyme, so that the growth of the bacteria is hindered. Besides, the narangin component synergies ascorbic acid, to improve the stability of ascorbic acid in the food. In addition, the narangin component has the action of stopping the growth of the malignant cell and the anticancer effect of recovering the cell being got damaged with the carcinogen.

The present inventor developed the suture which there is no problem to remain the nano-particle in the body with an antimicrobial activity, by applying the grapefruit extract containing the naringin component having such various functions to the suture, and the method of the same.

SUMMARY OF THE INVENTION

An aspect of the present invention provides a suture being capable of resolving the existing suture's problems, by minimizing the infection being capable of occurring when being surgery by applying the grapefruit extracts to the suture having an antibiotic effect and compensating the unsanitary part of the suture thread, and the method of the same.

BRIEF DESCRIPTION OF THE DRAWINGS

The above and other aspects, features and other advantages of the present invention will be more clearly understood from the following detailed description taken in conjunction with the accompanying drawings, in which:

FIG. 1 is a diagram that represents the coating process of the suture thread;

FIG. 2 is a FE-SEM analysis photograph of the suture thread according to one example of the present invention;

FIG. 3 is a SEM analysis photograph according to the time of the suture being contained in the grapefruit seed extract solution;

FIG. 4 is a UV-Vis analysis spectrum of the grapefruit seed extract according to one example of the present invention;

FIG. 5 is a graph that measures the amount of the grapefruit extract being contained in the suture according to the time;

FIG. 6 is a standard curve graph for the grapefruit extract solution;

FIG. 7 is a graph that represents the cumulative value of ppm concentration according to the time and measures the release of the grapefruit extract material of the suture that contains the grapefruit seed extract;

FIG. 8 is a graph and photo that represents the result of the antimicrobial test measuring the antimicrobial activity of the suture that contains the grapefruit extract according to one example of the present invention; and

FIG. 9 is a photograph that represents the degradation result of the suture that contains the grapefruit extract according to one example of the present invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

In order to achieve the aforementioned purpose, the present invention introduced the method of impregnating the suture to the grapefruit extract-containing solution for increasing the antibiosis.

In the above description, as the grapefruit extract, the extract that extracted from the seed of the grapefruit may be used, the grapefruit extract preferably includes naringin, ascorbic acid or citral component.

In addition, the suture may be made of biodegradable component, where the biodegradable component may be selected from the group consisting of PGA (polyglycolic acid), PLA (polylactic acid), PLLA (poly(lactide-co-L-lactide), PGLA (poly(glycolide-co-L-lactide), PG (polyglycolide), PL (polylactide) and a mixture thereof.

Furthermore, the suture may be made of unabsorbent component, where the unabsorbent component may be selected from the group consisting of polyester, nylon, PAN (polyacrylo nitrile) and a mixture thereof.

In addition, the suture has preferably the monofilament shape for the uniform containing of the grapefruit extract; the suture may further include calcium stearate as coating agent.

Meanwhile, in order to achieve the aforementioned purpose, the manufacturing method of the antimicrobial suture for medical use includes i) preparing the suture, and ii) impregnating the prepared suture to the grapefruit extract solution.

In the above, as the grapefruit extract solution, the methanol solvent is used; the concentration of the grapefruit extract solution is preferably 500 to 2000 ppm.

In addition, the suture is preferably impregnated to the grapefruit extract solution for more than 150 min. in order to secure the sufficient content of the grapefruit extract, however the experiment is proceeded for 360 min. that the optimal concentration is sufficiently impregnated.

The antimicrobial suture for medical use may prevent from the pathogen infection being occurred by the suture by providing the antimicrobial function to the suture by being contained the grapefruit extract having the antimicrobial effect into the suture. That is, the antimicrobial suture for medical use of the present invention improves the sanitation of the suture, prevent from the fungi generation on the surface of the suture that is main cause of the secondary infection being occurred when being surgery, and may stably maintain the strength and tension of the suture.

The antimicrobial suture for medical use containing the grapefruit extract and the manufacturing method thereof according to the present invention will now be described in detail with reference to the accompanying drawings.

The antimicrobial suture for medical use of the present invention is characterized in that contains the grapefruit extract.

In the above description, the suture may be made of biodegradable component, unabsorbent component or the mixture thereof, the biodegradable component may be selected from the group consisting of PGA (polyglycolic acid), PLA (polylactic acid), PLLA (poly(lactide-co-L-lactide), PGLA (poly(glycolide-co-L-lactide), PG (polyglycolide), PL (polylactide) and a mixture thereof, the unabsorbent component may be selected from the group consisting of polyester, nylon, PAN (polyacrylo nitrile) and a mixture thereof.

In addition, the grapefruit extract may use extract that is extracted from the seed of the grapefruit; the grapefruit extract includes naringin, ascorbic acid or citral component.

In the following example, the product of DF-100 on the market was used. The biodegradable suture has the property of being absorbed and degraded in the body, so that it is preferable to minimize the reaction with the water by using a methanol with strong evaporative power because the strength becomes weak and degradation is occur if it is exposed in water for a long time.

In addition, the suture has preferably the monofilament shape for the uniform containing of the grapefruit extract; the suture may further include calcium stearate as coating agent.

The monofilament is difficult to proliferate with the bacteria between the threads compared to the multifilament, as well as may decrease the main cause of infection being occurred when being surgery. In addition, in order to make up for the rough surface of the suture and the parasitic space of bacteria, the coating agent such as calcium stearate may be used.

Meanwhile, the manufacturing method of the antimicrobial suture for medical use includes i) preparing the suture, and ii) impregnating the prepared suture to the grapefruit extract solution.

FIG. 1 is a diagram that represents the coating process of the suture thread according to one embodiment of the present invention, the following chemical formula 3 is a reaction scheme regarding to the manufacture of the biodegradable monofilament suture being easy to procedure.

FIG. 2 is a FE-SEM analysis photograph of the suture according to one example of the present invention, after selecting the optimal polymerization composition ratio by comparing the physical property according to the polymerization composition ratio by spinning the prior selected polymer with various composition ratio under the same condition, the selected composition was prepared according to the spinning condition by using the monofilament spinner, to prepare the monofilament having excellent handling and knot stability.

The monofilament was tested according to the polymer constitution ratio by using the conjugated spinner again to prepare the optimal conjugated monofilament.

FIG. 3 is a SEM analysis photograph result being taken according to the time until 1 g of the prepared suture as above was placed into the 30 mL of the grapefruit extract 100 ppm solution and impregnated by the 30 minutes not to be absorb in the suture.

As seen in the drawings, there was no the thickness change of the suture due to contain the grapefruit extract of the suture, thus the inconvenient when using them could be minimized.

The present invention will now be described in detail with reference to the Example. However, the following Example is only intended to describe the present invention in detail, and the spirit and scope of the invention will not be limited by the following Example.

Example 1 Preparation of PGLA (Poly(Glycolide-co-L-Lactide))

The suture being used in the following examples was made through four processes largely. First of all, poly-glycolide and lactide were melted and made them to gel state, to mix with pigment, at this time, the melting and mixing process was performed by putting into the separately equipped melting and mixing bath in order to mix the pigment with gel state.

Then, the extruding process that opens and extrudes the valve being installed in each pressuring bath alternatively by pressurizing the raw material in the condition of the melt through each pressurizing bath, the spinning process that strongly extrudes the raw material being provided from the pressurizing bath in the form of thread through the spinning clamp, and the drawing process to increase the tensile strength and elasticity by drawing the spinned threads with the drawing apparatus were performed in turn.

FIG. 9 is a photograph that is taken the degradation behavior of 0.1 g of PGLA suture in the PBS solution for 10 days and 2 months respectively; we can confirm that the degradation of the suture was quickly progressed. The short degradation period refers that the biodegradation effect is high; it has advantage that the secondary infection due to the suture is decreased.

Example 2 Preparation of Grapefruit Extract

The experiment was proceeded with preparation of the grapefruit extract containing naringin component from 100 ppm to 1000 ppm. When impregnating the suture to the grapefruit extract, in order to prevent from the degradation phenomenon of the suture due to water, a methanol having high vaporizing degree was used as a solvent for resolving the grapefruit extract.

FIG. 4 represents the UV-VIS analysis result of the extract that measures in the wavelength of 283 nm by using JASCO V-550 UV-Vis Spectrophotometer (Wavelength Range: 200˜900 nm, Bandwidth Selectable: 0.5 nm, Scanning Speed 400 nm/min, Data Pitch 1 nm) analysis device. As seen the drawing, we could confirm that the inherent wavelength value was 283 nm.

Example 3 Impregnation to Grapefruit Extract Solution of Suture

After 1 g of the suture that was made in the example 1 and 30 mL of the grapefruit extract of 1000 ppm concentration that was made in the example 1 were put in vial and impregnated for 0 min., 30 min., 60 min., 90 min., 120 min., 150 min., 180 min., 240 min., 360 min., 420 min., 480 min., 540 min., 600 min., 660 min., 720 min., the suture was taken out and vacuum dried.

In order to confirm how much grapefruit extract were absorbed in the suture, UV-VIS analysis of the remaining solution was performed at 283 nm that is wavelength of naringin, and the amount of grapefruit extract being contained in the suture was shown in the graph of FIG. 5 according to the impregnating time.

As a measurement result, it could be confirmed that the amount of naringin being contained in the suture by 30 min. were the most, the content were not increased no longer after 150 min. With this, it could be confirmed that the minimal impregnating time was 150 min. and the reasonable content was shown more than 150 min. Because of this, the progress of the experiment was proceeded at 360 min.

Example 4 Measurements of Drug Release

The test for confirming the drug releasing degree in the body of the suture that contains naringin for 360 min. that was made in the example 3 was performed.

PBS (Phosphate Buffer Calculator, 0.01 M of Monobasic monohydrate: 1.1832 g, Dibasic ACS reagent: 8.1572 g) was prepared as a solvent for the present releasing test, and pH was adjusted to 7.4.

After drawing the standard curve of FIG. 6 with the grapefruit extract, the test was performed with preparation according to the each concentration. The standard curve for the functional material was obtained by measuring the absorbance by using JASCO V-550 UV-Vis Spectrometer (Wavelength Range: 200˜900 nm; Bandwidth Selectable: 0.5 nm; Scanning Speed: 400 nm/min; Data Pitch: 1 nm). The standard curve equation in FIG. 6 is as set below. x represents the concentration of the functional material, y represents the absorbance.

y=0.0015x−0.0348

After 1 g of the suture was taken and impregnated to the 30 mL grapefruit seed extract solution of 1000 ppm under stirring for 24 hours, it was filtered. The filtered suture was dried, 1 g of the dried suture was putted and PBS solution of 0.01 M was putted by 5 mL by using the pipette. Each sample was added to the shaker and extracted by 5 mL by using pipette for 2 hours, at this time the temperature was set to 36.5° C., and tested under the condition being similar to the temperature of the body.

FIG. 7 represents the result of the test and the release profile that the amount of time for release the grapefruit seed extract being contained in the suture could be confirmed.

Consequently, as a result of confirmation of the drug releasing of the suture that contains the grapefruit seed extract for 0˜150 hours, it could be confirmed that the drug releasing behavior was finished after about 70 hrs under the circumstance being almost same to the body. This may be expected that the antimicrobiotic power of the suture being putted in the body was maintained, and it could be confirmed that the damage of infection with the bacteria of the suture in the body due to this may be decreased.

Example 5 Antimicrobiosis

The antimicrobiotic power of the suture that contains the grapefruit seed extract of the example 3 was proceeded. As the used experiment method, the suture that contains the grapefruit seed extract was put to the microorganism culture of early logarithmic phase, then when the culture reacting with the suture that doesn't contain the grapefruit seed extract being used as the control was reached to the terminal logarithmic phase, 200 μl of cell culture was cultured for 24 hrs. at 30° C. by using the spread plate culture, then the number of colony that is formed by the strain was compared and measured. The used strain was Staphylococcus aureus.

FIG. 8 is a graph that represents the comparison of the antimicrobiotic power of the strain solution reacting with the suture that contains various mass of the grapefruit seed extract. It could be confirmed that the growth of the strain was suppressed by the grapefruit seed extract that was impregnated to the suture being injected into the cell sap, and the more the amount of the suture was increased, the more increased the antimicrobial power.

Particularly, it could be confirmed that the antimicrobial power of the grapefruit seed extract was high by confirming the antimicrobial power even at the small amount of 0.02% (w/v), the antimicrobial power of more than 99% was represented in the 1% (w/v) of the suture.

As set forth above, the antimicrobial suture for medical use of the present invention may prevent from the pathogen infection being occurred by the suture by providing the antimicrobial function to the suture by being contained the grapefruit extract having the antimicrobial effect into the suture. That is, the antimicrobial suture for medical use improves the sanitation of the suture, prevent from the fungi generation on the surface of the suture that is main cause of the secondary infection being occurred when being surgery, and may stably maintain the strength and tension of the suture.

While the present invention has been shown and described in connection with the exemplary embodiments, it will be apparent to those skilled in the art that modifications and variations can be made without departing from the spirit and scope of the invention as defined by the appended claims. 

1. An antimicrobial suture for medical use characterized in that a grapefruit extract is contained in the suture.
 2. The antimicrobial suture for medical use of claim 1, characterized in that the grapefruit extract is extracted from the grapefruit seed, includes naringin, ascorbic acid or citral component, and has the monofilament shape.
 3. The antimicrobial suture for medical use of claim 1, characterized in that the suture is made of biodegradable component, the biodegradable component is selected from the group consisting of PGA (polyglycolic acid), PLA (polylactic acid), PLLA (poly(lactide-co-L-lactide), PGLA (poly(glycolide-co-L-lactide), PG (polyglycolide), PL (polylactide) and a mixture thereof.
 4. The antimicrobial suture for medical use of claim 1, characterized in that the suture is made of unabsorbent component, the unabsorbent component is selected from the group consisting of polyester, nylon, PAN (polyacrylo nitrile) and a mixture thereof.
 5. A manufacturing method of an antimicrobial suture for medical use, comprising i) preparing the suture, and ii) impregnating the prepared suture to the grapefruit extract solution.
 6. The manufacturing method of an antimicrobial suture of claim 5, characterized in that the grapefruit extract solution uses a methanol solvent, the concentration of the grapefruit extract solution is 500 to 2000 ppm, and the suture is impregnated to the grapefruit extract solution for more than 360 min. 